1550例遗传咨询及细胞遗传学分析

目的 总结和探讨1550例遗传咨询者中染色体异常的发生情况。方法 抽取受检者外周血,常规微量法培养及制备染色体标本,G显带运动核型分析。结果 在1550例受检查中共检出染色体异常87例,异常率为5．61％。其中有不良孕产史者833例中,染色体异常34例;不孕不育症109例中,染色体异常8例;闭经及性腺发育不良102例中,染色体异常19例,智能发育不全者172例中,染色体异常24例,其它334例中,染色体异常2例。结论 染色体异常与许多生育及发育缺陷有关,对这些患者进行染色体检查以明确诊断很有必要。     

364例遗传咨询者细胞遗传学及临床分析

目的：探讨遗传咨询者的染色体异常与临床异常的关系。方法本文对本科前来遗传咨询的364例咨询者资料进行分析,采用染色体G显带技术进行分析。结果遗传咨询的364例患者中,染色体核型异常为54例,检出率14.83%,有120例患者智力低下,发育迟缓、其异常核型有12例（10%）、104例不良孕产史,其中8例异常核型（占7.7%）,43例不孕不育,7例异常核型（16.2%）等。结论孕妇体内染色体发生异常时会造成新生儿智力低下、不孕不育、两性畸形等疾病,因此临床上应该从遗传咨询者进行细胞遗传学分析,采取有效措施进行预防,从而实现优生优育。     

CDH1基因甲基化状态与结直肠癌临床病理特征及预后的相关性分析

目的 检测原发性结直肠癌患者术中腹腔灌洗液悬浮细胞中的CDH1基因启动子所在5''-CpG岛的异常甲基化,同时对其异常甲基化与临床病情发展、病理变化及术后预后的相关关系进行探讨。 方法 选取该院肿瘤科进行结直肠癌切除术的原发性结直肠癌患者,所有入选患者由专人进行跟踪随访。检测CDH1基因启动子所在5''-CpG岛的异常甲基化,对其异常甲基化与临床病情发展、病理变化及术后预后的相关关系进行探讨。 结果 该研究共纳入患者184例,其中甲基化组86例,非甲基化组98例。对两组患者临床病理结果检查可知甲基化组肿瘤直径大于非甲基化组(P＜0.001),甲基化组肿瘤浸润性所占比例高于非甲基化组(P＜0.001),甲基化组肿瘤分化程度低于非甲基化组(P＜0.001),甲基化组淋巴转移率、远处转移率高于非甲基化组(P＜0.001,P=0.026),甲基化组临床TNM分期更晚(P＜0.001)。根据随访结果显示非甲基化组患者生存率高于甲基化组患者(P＜0.05)。Cox比例风险模型结果显示,患者肿瘤的大体分型、分化程度、侵袭程度和病理分期是影响生存预后的变量,其中腹腔灌洗液悬浮细胞CDH1基因甲基化是影响预后最重要的独立因素,RR=28.514。 结论 原发性结直肠癌患者腹腔灌洗液悬浮细胞CDH1基因甲基化程度提高,恶性程度高,预后差。     

低形态学评分卵裂期胚胎的X、Y及18号染色体分析

目的:分析低形态学评分的D3卵裂期胚胎X、Y及18号染色体的非整倍体情况。方法:收集体外受精-胚胎移植术后剩余的废弃胚胎,胚胎固定后采用荧光原位杂交技术检测细胞核内的X、Y及18号染色体。结果:共收集废弃胚胎60个,其中正常胚胎29个,18号染色体异常胚胎12个,X/Y染色体异常胚胎8个,18、X/Y染色体均异常胚胎11个。观测到荧光信号的细胞核有233个,其中正常细胞核115个(49.4%),异常细胞核118个(50.6%)。18号染色体非整倍体率40.8%,X/Y染色体非整倍体率33.5%,差异无统计学意义(χ2=2.65,P>0.05)。18号染色体三体发生率(21.9%)与X/Y染色体三体发生率(12.0%)差异有统计学意义(χ2=11.58,P<0.01)。结论:D3形态评分低的胚胎有相当大的比例存在染色体异常,通用的胚胎形态学评分系统能够在一定程度上反映胚胎的染色体情况。     

产前诊断中染色体异常核型的细胞遗传学及临床分析

目的 探讨产前诊断中染色体异常核型的细胞遗传学及临床特点,以期为后期产前诊断工作提供经验.方法 回顾性分析407份开展孕早期绒毛及孕中期羊水染色体检查孕妇的绒毛组织或羊水样本,观察染色体异常核型样本产前指征分布状况及染色体异常核型样本分布情况、临床特点.结果 407份样本中,染色体异常核型24份(5.90％),其中1份...     

HPV-DNA检测对宫颈癌诊断的临床指导

目的探讨检查女性生殖道感染HPV-DNA对诊断宫颈癌临床指导意义。方法选择2860例宫颈炎患者,随机分两组,一组用传统宫颈刮片法检测,一组用HPV-DNA＋宫颈刮片法检测。结果用HPV-DNA＋宫颈刮片法检测率达98.5%,用传统宫颈刮片法检测率73%。结论 HPV-DNA检测可提高宫颈癌诊断。     

急性白血病患者的染色体核型分析及临床意义

目的结合细胞形态学、免疫学探讨染色体核型在急性白血病(AL)中的诊断、治疗价值。根据国内外细胞遗传学危险度划分标准,分析核型与完全缓解率(CR)的相关性。方法采用短期培养法处理骨髓样本,并以R显带为主,G显带为辅,对119例初诊的AL患者进行染色体核型分析,并观察患者CR与染色体核型分析之间的关系。结果患者核型率异常在急性髓细胞白血病(AML)、急性淋巴细胞白血病(ALL)中分别为58.11%、53.33%,平均异常率为56.30%,AML患者中最常见的平衡易位为46,XY,t(15;17)(q22;q21),占所分析患者的19.33%(23/119),且仅在M3中检测到,其次是t(8;21)(q22;q22),占10.08%(12/119)。在ALL患者中最常见的为t(9;22)(q34;q11),且多见于B-ALL,占6.72%。119例患者中首次化疗CR达71.43%,特异性染色体核型的患者CR较高。结论染色体检查技术结合细胞形态学、免疫表型分析对于白血病的准确诊断、靶向治疗、评估预后具有重要意义。     

胃癌组织中人类表皮生长因子受体2的表达及与临床病理特征的相关性分析

目的检测胃癌组织中的人类表皮生长因子受体(HER)-2蛋白和HER-2基因的表达,探讨其与胃癌患者临床病理特征的关系。方法采用免疫组织化学法(IHC)检测115例胃癌活检标本中的HER-2蛋白表达,对HER-2蛋白过表达(IHC评分为++和+++)的标本采用荧光原位杂交技术(FISH)检测其HER-2基因水平和17号染色体倍体分析。结果①115例胃癌标本中,HER-2蛋白过表达率为40.0%(46/115)。HER-2蛋白的过表达与胃癌的Lauren分型、分化程度、浸润深度、淋巴结转移有关(P<0.05),与患者的年龄、性别、肿瘤大小、肿瘤部位等因素无关(P>0.05)。②HER-2基因的扩增率在HER-2蛋白(+++)组为90.5%(19/21),明显高于HER-2蛋白(++)组28.0%(7/25),差异有统计学意义(P<0.05)。③17号染色体多体在HER-2蛋白(++)组和(+++)组中的发生率分别为36.0%(9/25)和47.6%(10/21),差异无统计学意义(P>0.05)。结论①HER-2蛋白过表达的肿瘤细胞存在17号染色体多倍体现象,提示17号染色体多倍体可能引起HER-2蛋白过表达。②HER-2蛋白的过表达和HER-2基因的扩增与胃癌发生发展密切相关,这将为临床预测胃癌的预后及选择性靶向治疗提供理论依据。     

产前诊断22号染色体三体嵌合1例并文献复习

目的 总结22号染色体三体嵌合的临床特征,提高对22号染色体三体嵌合的产前诊断及遗传咨询水平.方法 回顾性分析2018年就诊于安徽省立医院产前诊断中心确诊为22号染色体三体嵌合胎儿的病例1例,并检索相关文献,总结主要临床特征.结果 病人28岁,17+6周无创DNA检测提示22号染色体三体高风险,孕18周产前超声筛查提示...     

Establishment of a protocol for the gene expression analysis of laser microdissected rat kidney samples with affymetrix genechips

Laser microdissection in conjunction with microarray technology allows selective isolation and analysis of specific cell populations, e.g., preneoplastic renal lesions. To date, only limited information is available on sample preparation and preservation techniques that result in both optimal histomorphological preservation of sections and high-quality RNA for microarray analysis. Furthermore, amplification of minute amounts of RNA from microdissected renal samples allowing analysis with genechips has only scantily been addressed to date. The objective of this study was therefore to establish a reliable and reproducible protocol for laser microdissection in conjunction with microarray technology using kidney tissue from Eker rats p.o. treated for 7 days and 6 months with 10 and 1mg Aristolochic acid/kg bw, respectively. Kidney tissues were preserved in RNAlater or snap frozen. Cryosections were cut and stained with either H&E or cresyl violet for subsequent morphological and RNA quality assessment and laser microdissection. RNA quality was comparable in snap frozen and RNAlater-preserved samples, however, the histomorphological preservation of renal sections was much better following cryopreservation. Moreover, the different staining techniques in combination with sample processing time at room temperature can have an influence on RNA quality. Different RNA amplification protocols were shown to have an impact on gene expression profiles as demonstrated with Affymetrix Rat Genome 230_2.0 arrays. Considering all the parameters analyzed in this study, a protocol for RNA isolation from laser microdissected samples with subsequent Affymetrix chip hybridization was established that was also successfully applied to preneoplastic lesions laser microdissected from Aristolochic acid-treated rats.     

Gene profiles of a human bronchial epithelial cell line after in vitro exposure to respiratory (non-)sensitizing chemicals: Identification of discriminating genetic markers and pathway analysis

Respiratory sensitization is a concern for occupational and environmental health in consumer product development. Despite international regulatory requirements there is no established protocol for the identification of chemical respiratory sensitizers. New tests should be based on mechanistic understanding and should be preferentially restricted to in vitro assays. The major goal of this study was to investigate the alterations in gene expression of human bronchial epithelial (BEAS-2B) cells after exposure to respiratory sensitizers and respiratory non-sensitizing chemicals, and to identify genes that are able to discriminate between both groups of chemicals. BEAS-2B cells were exposed during 6, 10, and 24 h to the respiratory sensitizers ammonium hexachloroplatinate IV, hexamethylene diisocyanate, and trimellitic anhydride, the irritants acrolein and methyl salicylate, and the skin sensitizer 1-chloro-2,4-dinitrobenzene. Overall changes in gene expression were evaluated using Agilent Whole Human Genome 4× 44K oligonucleotide arrays. Fisher Linear Discriminant Analysis was used to obtain a ranking of genes that reflects their potential to discriminate between respiratory sensitizing and respiratory non-sensitizing chemicals. The 10 most discriminative genes were BC042064, A_24_P229834, DOCK11, THC2544911, DLGAP4, NINJ1, PFKM, FLJ10986, IL28RA, and CASP9. Based on the differentially expressed genes, pathway analysis was used to identify possible underlying mechanisms of respiratory sensitization. We demonstrated that in bronchial epithelial cells the canonical PTEN signaling pathway is probably the most specific pathway in the context of respiratory sensitization. Results are indicative that the BEAS-2B cell line can be used as an alternative cell model to screen chemical compounds for their respiratory sensitizing potential.     

Timely awareness and prevention of emerging chemical and biochemical risks in foods: Proposal for a strategy based on experience with recent cases

A number of recent food safety incidents have involved chemical substances, while various activities aim at the early identification of emerging chemical risks. This review considers recent cases of chemical and biochemical risks, as a basis for recommendations for awareness and prevention of similar risks at an early stage. These cases include examples of unapproved genetically modified food crops, intoxications with botanical products containing unintentionally admixed toxic herbs, residues of unapproved antibiotics and contaminants in farmed aquaculture species such as shrimp and salmon; and adverse effects of chemical and biological pesticides of natural origin. Besides case-specific recommendations for mitigation of future incidents of the same nature, general inferences and recommendations are made. It is recommended, for example, to establish databases for contaminants potentially present within products. Pro-active reconnaissance can facilitate the identification of products potentially contaminated with hazardous substances. In international trade, prevention and early identification of hazards are aided by management systems for product quality and safety, rigorous legislation, and inspections of consignments destined for export. Cooperation with the private sector and foreign authorities may be required to achieve these goals. While food and feed safety are viewed from the European perspective, the outcomes also apply to other regions.     

3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C,Nanopore, and RNA sequencing

The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.